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Epithelial Cell-Derived IL-25, but Not Th17 Cell-Derived IL-17 or IL-17F, Is Crucial for Murine Asthma

Citation

Suzukawa, M and Morita, H and Nambu, A and Arae, K and Shimura, E and Shibui, A and Yamaguchi, S and Suzukawa, K and Nakanishi, W and Oboki, K and Kajiwara, N and Ohno, T and Ishii, A and Korner, H and Cua, DJ and Suto, H and Yoshimoto, T and Iwakura, Y and Yamasoba, T and Ohta, K and Sudo, K and Saito, H and Okumura, K and Broide, DH and Matsumoto, K and Nakae, S, Epithelial Cell-Derived IL-25, but Not Th17 Cell-Derived IL-17 or IL-17F, Is Crucial for Murine Asthma, Journal of Immunology, 189, (7) pp. 3641-3652. ISSN 0022-1767 (2012) [Refereed Article]

Copyright Statement

Copyright 2012 The American Association of Immunologists

DOI: doi:10.4049/jimmunol.1200461

Abstract

IL-17A, IL-17F, and IL-25 are ligands for IL-17RA. In the current study, we demonstrated that IL-25-deficient mice-but not IL-17A-, IL-17F-, IL-17A/F-, IL-23p19-, or retinoic acid-related orphan receptor (ROR)-γt-deficient mice-showed significant suppression of 1) the number of eosinophils and the levels of proinflammatory mediators in bronchoalveolar lavage fluids, 2) airway hyperresponsiveness to methacholine, and 3) OVA-specific IgG1 and IgE levels in the serum during OVA-induced Th2-type/eosinophilic airway inflammation. The IL-25 deficiency did not affect lung dendritic cell migration or Ag-specific memory-Th2 cell expansion during Ag sensitization. Adoptive transfer of T cells, mast cells, or bone marrow cells from IL-25-deficient mice revealed that induction of Th2-type/eosinophilic airway inflammation was dependent on activation of lung epithelial cells and eosinophils by IL-25 produced by airway structural cells such as epithelial cells but not by such hematopoietic stem-cell-origin immune cells as T cells and mast cells. Therefore, airway structural cell-derived IL-25-rather than Th17 cell-derived IL-17A and IL-17F-is responsible for induction of local inflammation by promoting activation of lung epithelial cells and eosinophils in the elicitation phase of Th2-type/eosinophilic airway inflammation. It is not required for Ag-specific Th2 cell differentiation in the sensitization phase.

Item Details

Item Type:Refereed Article
Research Division:Medical and Health Sciences
Research Group:Immunology
Research Field:Immunology not elsewhere classified
Objective Division:Expanding Knowledge
Objective Group:Expanding Knowledge
Objective Field:Expanding Knowledge in the Medical and Health Sciences
Author:Korner, H (Professor Heinrich Korner)
ID Code:80705
Year Published:2012
Web of Science® Times Cited:51
Deposited By:Menzies Institute for Medical Research
Deposited On:2012-11-08
Last Modified:2013-07-02
Downloads:0

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